A total of 281 non-duplicated Staphylococcus aureus blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant S. aureus (MRSA). Cefoxitin-disk diffusion tests and mecA gene PCR revealed that 56.6% (159/281) of S. aureus was MRSA and mostly belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) was non-susceptible to ceftaroline (MIC ≥2 mg/L), whereas all of the methicillin-susceptible S. aureus isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1-2 mg/L, two or three substitutions at 2-4 mg/L, and five substitutions at 4 or 16 mg/L. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and in nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.
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